Furthermore, AD-PRS-related atrophy was independent of age, sex, education and vascular risk scores, and not evident for regions that show non-Alzheimer's disease-related atrophy with age, consistent with a cross-sectional study.28 This suggests that APOE-ɛ4 and other AD risk genes influence atrophy in common Alzheimer's disease-susceptible brain regions, including the hippocampus, as early as midlife. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.